The Differential Expression of Long Noncoding RNAs in Type 2 Diabetes Mellitus and Latent Autoimmune Diabetes in Adults.

Zhang Pengyu,Fu Xiying,Yang Maoguang,Li Mo,Shen Hong,Cheng Yan,Wang Lijuan,Cai Hanqing,Yan Yan,Zhang Xiujuan

doi:10.1155/2020/9235329

Abstract

Background Long noncoding RNAs (lncRNAs) were previously found to be closely related to the pathogenesis of diabetes. Objectives To reveal the differentially expressed lncRNAs and messenger RNAs (mRNAs) involved in type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADA) and predict the lncRNA target genes to derive their expression profiles for the diagnosis of T2DM and LADA and their differential diagnosis. Methods Twelve venous blood samples were collected from T2DM patients, LADA patients, and nondiseased subjects to obtain total RNAs. After removing rRNA from total RNAs to establish the desired library for sequencing, quality control and quantification analyses were carried out. The fragments per kilobase of exon model per million reads mapped (FPKM) of lncRNAs were calculated to construct the gene expression profiles of lncRNAs and mRNAs. Fold changes (fold change: 2.0) and p values (p values (Results Compared to nondiseased controls, 68,763 versus 28,523 lncRNAs and 133 versus 1035 mRNAs were significantly upregulated and significantly downregulated, respectively, in T2DM patients. For LADA patients, 68,748 versus 28,538 lncRNAs and 219 versus 805 mRNAs were significantly upregulated and significantly downregulated, respectively, relative to nondiseased controls. Compared to T2DM patients, 74,207 versus 23,079 lncRNAs and 349 versus 137 mRNAs were significantly upregulated and significantly downregulated, respectively, in LADA patients. Based on the correlation analysis, seven lncRNA-mRNA pairs (BTG2, A2M, HECTD4, MBTPS1, DBH, FLVCR1, and NCBP2) were significantly coexpressed, and two lncRNAs (ENST00000608916 and ENST00000436373) were newly discovered. Conclusion Significant differences in lncRNA expression were discovered among the three groups. Furthermore, after predicting lncRNA expression profiles, GO/KEGG pathway analysis could deduce the target gene function.

Highlights

Adult onset, slow progression, and evidence of damage to one or more islet autoantibodies serve as the three major characteristics of latent autoimmune diabetes in adults (LADA). e autoimmune process of LADA is slower than that of the classical type 1 diabetes mellitus (T1DM) and new therapeutic interventions might cause a delay in ß cell failure
As Long noncoding RNAs (lncRNAs) are closely related to the pathogenesis of diabetes [6], we aimed to reveal the differential expression of lncRNAs and messenger RNAs (mRNAs) in type 2
Samples were collected in advance. ereafter, we applied for an exemption from informed consent and obtained approval from the Ethics Committee. e diagnostic criteria included patients diagnosed with diabetes according to the World Health Organization criteria. e selection criteria for the LADA group were patients diagnosed with diabetes between 30 and 55 years of age who were insulin-independent for at least 6 months after diagnosis and positive for glutamate decarboxylase autoantibodies (GAD Ab) or tyrosine phosphatase autoantibodies (IA2 Ab)

Summary

Introduction

Adult onset, slow progression, and evidence of damage to one or more islet autoantibodies serve as the three major characteristics of latent autoimmune diabetes in adults (LADA). e autoimmune process of LADA is slower than that of the classical type 1 diabetes mellitus (T1DM) and new therapeutic interventions might cause a delay in ß cell failure. As lncRNAs are closely related to the pathogenesis of diabetes [6], we aimed to reveal the differential expression of lncRNAs and mRNAs in type 2. To reveal the differentially expressed lncRNAs and messenger RNAs (mRNAs) involved in type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADA) and predict the lncRNA target genes to derive their expression profiles for the diagnosis of T2DM and LADA and their differential diagnosis. 68,763 versus 28,523 lncRNAs and 133 versus 1035 mRNAs were significantly upregulated and significantly downregulated, respectively, in T2DM patients. For LADA patients, 68,748 versus 28,538 lncRNAs and 219 versus 805 mRNAs were significantly upregulated and significantly downregulated, respectively, relative to nondiseased controls. Compared to T2DM patients, 74,207 versus 23,079 lncRNAs and 349 versus 137 mRNAs were significantly upregulated and significantly downregulated, respectively, in LADA patients. After predicting lncRNA expression profiles, GO/KEGG pathway analysis could deduce the target gene function

Objectives

Methods

Results

Conclusion